One stop diagnostics for febrile illnesses in Crimean-Congo Haemorrhagic Fever endemic settings

This PhD opportunity is being offered as part of the LSTM and Lancaster University Doctoral Training Partnership. Find out more about the studentships and how to apply

Abstract Crimean-Congo Haemorrhagic Fever (CCHF) emerged in Turkey in 2002. To date, Turkey is the CCHF endemic country with higher numbers of reported cases, reaching >1000 annually with a mortality rate of approximately 30%. CCHF virus (CCHFV) is transmitted by a tick of the genus Hyalomma and has a seasonal epidemiology. During CCHF season (spring to summer period in Turkey) 50% of the patients that present with early CCHF symptomatology to the clinics are positive while <10% are during non-CCHFV season. Early symptomatology of CCHFV infection is characterised by non-specific febrile illnesses and symptoms (headache, myalgia, weakness, nausea, vomiting, abdominal pain, and diarrhoea) are similar to other endemic infection diseases such as brucellosis, leptospirosis, rickettsiosis, viral hepatitis, Q fever, or potentially other viral haemorrhagic fevers. Diagnosis for CCHF is currently only performed in reference laboratories, and this causes a delay of 2-6 days in obtaining the results. This delay is hampering patient management in patients that are waiting for a CCHF result. As early CCHF symptomatology is non-specific, this diagnostic delay also affects patient management in patients with other endemic febrile illnesses that are suspected but negative to CCHF infection. In addition to this, the aetiology of the infections in CCHF negative patients often does not get further investigated and cause of infection remains undiagnosed.
The aims for this project are to investigate the pathogens that infect patients who are suspected with CCHF infection but test CCHF negative and the development of a multiplex point-of-care test for rapid diagnosis of CCHF together with the most prevalent diseases with similar presentation. The aim of this PhD project is to accelerate rapid diagnosis of febrile patients to improve patient management in CCHF endemic settings.
This project involves performing sequencing of serum samples collected from patients attending clinics with suspected CCHF infection during CCHF and no CCHF season to identify what pathogens with similar symptomatology to CCHF are circulating and develop a multiplex point-of-care diagnostic assay (PCR or immunoassay) to diagnose most prevalent febrile illness in one step. The endemic country of study will be Turkey with scope to investigate further endemic regions such as Senegal.
The supervisory team includes members with laboratory and clinical experience and the candidate will have the opportunity to travel to the country partners to work closely with our long-term collaborators in this project.
Where does this project lie in the translational pathway? T1 - Basic Research,T2 - Human /Clinical Research
Expected Outputs The expected outcomes of this project are publications of high public health impact which will be relevant for the scientific community working with CCHF and other febrile illness. Epidemiological findings on the aetiology of febrile illness in CCHF endemic regions. Development of a diagnostic assay for multiplex detection of a panel of febrile illness pathogens. The developed multiplex test will have the potential to lead to further progress through the development pipeline for commercialisation.
Training Opportunities Pilot data will be used to encourage the candidate to apply for fellowship applications for career development. The proof of concept will be used to apply for funding to progress the assay into the development pipeline towards commercialisation.
Skills Required An ideal candidate should have a strong molecular biology background and/or computational skills in bioinformatics, but training will be provided. We expect the student to possess strong organisational and project-solving aptitudes with good inter-personal skills.

Key Publications associated with this project

Cubas-Atienzar, A. I., Kontogianni, K., Edwards, T., Wooding, D., Buist, K., Thompson, C. R., ... & Adams, E. R. (2021). Limit of detection in different matrices of 19 commercially available rapid antigen tests for the detection of SARS-CoV-2. Scientific reports, 11(1), 18313.
  Cubas-Atienzar, A. I., Williams, C. T., Karkey, A., Dongol, S., Sulochana, M., Rajendra, S., ... & Edwards, T. (2021). A novel air-dried multiplex high-resolution melt assay for the detection of extended-spectrum β-lactamase and carbapenemase genes. Journal of Global Antimicrobial Resistance, 27, 123-131.
  Byrne, R. L., Aljayyoussi, G., Greenland-Bews, C., Kontogianni, K., Wooding, D., Williams, C. T., ... & Cubas-Atienzar, A. I. (2023). Comparison of the analytical and clinical sensitivity of thirty-four rapid antigen tests with the most prevalent SARS-CoV-2 variants of concern during the COVID-19 pandemic in the UK. medRxiv, 2023-07.
  Bower, H., El Karsany, M., Alzain, M., Gannon, B., Mohamed, R., Mahmoud, I., ... & Fletcher, T. E. (2019). Detection of Crimean-Congo Haemorrhagic Fever cases in a severe undifferentiated febrile illness outbreak in the Federal Republic of Sudan: A retrospective epidemiological and diagnostic cohort study. PLoS neglected tropical diseases, 13(7), e0007571.
  Bozkurt, I. (2024). We Need More Accuracy in Crimean-Congo Hemorrhagic Fever Diagnosis upon Initial Presentation in Endemic Areas. Vector-Borne and Zoonotic Diseases.